This K05 Senior Scientist Award is to support Dr. Jean M. Bidlack's research activities. The specific aim of this award is to provide Dr. Bidlack with some release time from grant writing, teaching and administrative responsibilities to cover her salary. This award will allow her to devote the majority of her time to research and the training of graduate students and postdoctoral fellows. Training activities will be supported by a NIDA Training Grant (T32 DA07232). Dr. Bidlack will expand her research background and expertise in studying the expression and regulation of opioid receptors on immune cells. Also, she will investigate whether a chemokine receptor expressed on human herpes virus -6 and -7 binds opioids, and if opioids alter chemokine activation of the receptor. This chemokine receptor, U51, shares considerable amino acid sequence homology and similarity with the kappa opioid receptor. In addition, ongoing studies directed at medications development for the treatment of heroin and cocaine abuse will continue. The working hypothesis for which we have produced experimental support is that compounds, which release dopamine from the nucleus accumbens, promote drug-seeking behavior and those, which prevent release of this transmitter, prevent drug-seeking behavior. It is known that kappa agonists and mu antagonists inhibit dopamine release in the nucleus accumbens. Studies are further defining properties of select compounds that make some ? agonists with varying activity at mu receptors better at reducing cocaine self-administration in nonhuman primates than other compounds. In collaboration with chemists and behaviorists, we are evaluated new opioids as potential pharmacotherapeutics for treating drug abuse. The goals of these three independent projects will be accomplished within the framework of two R01 grants, a R21 grant, and three subcontracts from NIDA. Collectively, these projects will provide new information on the localization and function of the multiple opioid receptors on immune cells and on the human herpes viruses -6 and -7. Also, they will advance efforts in developing drugs to treat cocaine and heroin abuse. The present proposal is being requested in order to provide the candidate with stability of support, which is necessary for her continued commitment to research in the field of drug abuse and to ensure her sustained high level of productivity as both a senior scientist, and as a mentor for trainees, who will be the next generation of drug abuse researchers.